The proposed research is a study of the relationship between mammary tumor cell surface properties and the tumorigenicity and metastasis of the cells in a syngeneic host. Several tumor cell variant subpopulations have been isolated from the transplantable 13762 rat mammary adenocarcinoma by cloning and selection in vitro. The metastatic variants will be characterized in vivo by analysis of tumor growth at subcutaneous injection sites, short-term cell survival and organ selectivity of tumor cell arrest following injection of (125I) iododeoxyuridine-labeled cells, and patterns of long-term metastatic growth. Characterization in vitro will emphasize aspects of cell adhesiveness, to be defined by measurements of adhesion to substratum, self-aggregation, and attachment to monolayers of rat fibroblasts and endothelial cells. In biochemical studies of cell surface macromolecular composition and organization, glycoproteins, proteoglycans, antigens, and lectin-binding proteins will be identified by radiolabeling, enzymatic dissection, immunoprecipitation, and specific ligand binding; these components will be partially characterized by gel electrophoresis, and their patterns of organization will be determined using protein cross-linking reagents. The kinetics and selectivity of tumor cell surface shedding will be studied in vitro. Several variants differing in metastatic activity will be examined, so that results of biochemical analysis and in vitro characterization can be correlated with patterns of mammary tumor cell behavior in vivo.